Evidence that 3α-hydroxy-5α-pregnan-20-one is a physiologically relevant modulator of gaba-ergic neurotransmission

3α-Hydroxy-5α-pregnan-20-one (HPO) is a progesterone metabolite which exhibits narcotic properties at high concentrations by interactions with the receptor for gamma-aminobutyric acid (GABA). The present investigation characterized low-dose effects of HPO on GABA_A receptor binding, by determining the allosteric properties of HPO on the in vitro binding of ³H-muscimol to membrane fractions from the cerebella of ovariectomized rats. A newly developed method for tissue preparation was used to wash out endogenous ligands interfering with the assay. HPO reduced the affinity of ³H-muscimol to GABA_A receptor sites by 52% and enhanced the number of accessible binding sites from 5.5±0.5 to 7.5±1.3 pmol/mg protein at subnanomolar (0.1 nM) HPO concentrations. The modulatory effects of HPO on GABA_A receptor binding provide evidence that this pregnane steroid might be a physiologically relevant modulator of GABAergic neurotransmission.     

Epidemiology of acute diarrhea in children living in Sicily

A longitudinal survey (February 1984 - January 1985) on the incidence of acute diarrhea episodes in a sample of 8,164 children (aged 0–12 years) living in southeastern Sicily was carried out by means of weekly telephone interviews with doctors practising in the territory. The incidence rate was 0.479 (0.472–0.485 95% C.I.) per child per year and the frequency of episodes was significantly higher (p < 0.001) in children aged 0–4 years (0.86). Diarrhea was more frequent in industrial areas than in rural ones, and almost half (45.1%) of the total episodes had a mild course. No death from diarrhea occurred and admission to hospital was reported for 8.4% of all cases.Corresponding author.     

Bone loss and forms of tibial condylar fracture

Summary Bone loss and fracture type were determined in 358 tibial condylar fractures. Degree of osteoporosis at the knee was defined by analogy to Singh's grades of osteoporosis at the hip and to Jhamaria's classification of osteoporosis at the calcaneum: grade V — normal; grade IV — slight reduction of trabecular bone; grade III — osteoporosis, predominantly of trabecular bone; grade II — osteoporosis of trabecular and cortical bone. Five fracture types were distinguished, with the component of trabecular bone compression increasing from a to e: a — pure split fractures; b — split fractures with displacement of a piece of the articular surface; c — split compression fractures; d — local compression fractures; e — compression of a whole condyle. There was a highly significant rank correlation between the two sets of ordered categories. Fractures in osteoporotics tended to involve the lateral condyle; this is explained by the fact that crush fractures occurred more frequently at the lateral condyle. The influence of bone loss on fracture type was demonstrated to be independent of age. A clear understanding of these associations concerning three variables at a time was reached by the use of log-linear-model analysis for cross-classified qualitative data.

---

Zusammenfassung Bei 358 Frakturen der proximalen Tibia wurden der röntgenologisch erkennbare Knochenschwund und die Frakturform festgestellt. Entsprechend dem Singh-Index zur Bestimmung der Osteoporose am proximalen Femur und der Klassifikation der Trabekelstruktur am Fersenbein nach Jhamaria wurden folgende Osteoporosegrade am Knie definiert: Grad V — normal, Grad IV — Spongiosastruktur leicht vermindert, Grad III — Osteoporose betrifft vorwiegend die Spongiosa, Grad II —Osteoporose von Spongiosa und Kompakta. Fünf Frakturformen wurden unterschieden, wobei das Ausmaß der Spongiosakompression von a bis e ansteigt: a — reine Spaltfrakturen, b — Spaltfrakturen mit Abscherung eines Gelenkflächenteiles, c —Spaltkompressionsfrakturen, d — Frakturen mit lokaler Kompression, e — Frakturen mit Kompression eines ganzen Kondyls. Zwischen diesen beiden Merkmalen, deren Ausprägungen Rangklassen bilden, war eine hochsignifikante Rangkorrelation nachzuweisen. Brüche osteoporotischer Knochen betrafen vermehrt den lateralen Gelenksknorren, was dadurch statistisch zu erklären war, daß dieser sich für Kompressionsfrakturen als anfälliger erwies. Die Beziehung zwischen Osteoporose und Frakturform war nicht abhängig vom Lebensalter. Solche Zusammenhange zwischen je drei Variablen konnten übersichtlich dargestellt wurden, indem die Häufigkeitstabellen durch Log-lineare Modelle interpretiert wurden.

     

Adenocarcinoma of the lower esophagus. A disease primarily of white men with Barrett's esophagus

Sex and racial predilection, social history, and histology were analyzed in a biopsy-proven adenocarcinoma of the lower esophagus/esophagogastric junction collected over a 5-year period in two teaching institutions with different patient populations. Adenocarcinoma occurred in 11% of patients with biopsy-proven esophageal cancer. The disease occurred only in males at one center, and in a 7:1 ratio of males to females at the other center. Clear racial predilection was seen, since 12 of 13 patients with adenocarcinoma of the esophagus were white, whereas less than 20% of patients with squamous carcinoma of the esophagus were white. The finding of Barrett's epithelium in eight of the 13 cases strongly supports the theory that in white males, Barrett's epithelium is a precursor lesion of adenocarcinoma of the esophagus/esophagogastric junction.